Koç, Alparslan; Gazi, Mustafa; Caner Sayar, Ali; Onk, Didem; Ali Arı, Muhammet; Süleyman, Bahadır; Gökhan Ağgül, Ahmet; Altındağ, Fikret; Altuner, Durdu; Süleyman, Halis

Toxic doses of paracetamol are also known to be close to therapeutic doses. This study aimed to biochemically investigate the protective effect of ATP against paracetamol-induced oxida-tive liver injury in rats and to examine the tissues histopathologically. We divided the animals into the paracetamol alone (PCT), ATP + paracetamol (PATP), and healthy control (HG) groups. Liver tissues were examined biochemically and histopathologically. Malondialdehyde level, AST and ALT activity in the PCT group were significantly higher than those in the HG and PATP groups (p < 0.001). The glutathione (tGSH) level, superoxide dismutase (SOD) and catalase (CAT) activity in the PCT group was significantly lower than that in the HG and PATP groups (p < 0.001), while animal SOD activity was significantly different between the PATP and HG groups (p < 0.001). The activity of CAT was almost the same. In the group treated with paracetamol alone, lipid deposition, necrosis, fibrosis, and grade 3 hydropic degeneration were observed. No histopathological damage was observed of the ATP-treated group, except for grade 2 edema. We discovered that ATP reduces the oxidative stress caused by paracetamol ingestion and protects against paracetamol-induced liver injury at the macroscopic and histological levels.

Koç, Alparslan; Kuyrukluyildiz, Ufuk; Gazi, Mustafa; Sayar, Ali Caner; Altuner, Durdu; Süleyman, Halis; Yavuzer, Bülent; Çoban, Taha Abdulkadir; Süleyman, Zeynep; Yazici, Gülce Naz

The primary sources of reactive oxygen species (ROS) that cause ischemia-reperfusion (I/R) injuries are enzymes xanthine oxidase (XO) and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in the literature, whereby one of the main ROS producing cells via NOX activity are polymophonuclear leukocytes (PNL). Sugammadex, the effect of which we plan to research against gastric I/R damage, is a modified gamma-cyclodextrin that antagonizes the action of steroidal neuromuscular blocking drugs. Previous studies have reported that sugammadex inhibits PNL infiltration. However, it is unknown whether an inhibitory effect on XO is present. We aimed to biochemically and histopathologically investigate the effects of sugammadex on I/R-induced stomach damage in rats. The animals were divided into groups that underwent gastric ischemia-reperfusion (GIR), 4 mg/kg sugammadex + gastric ischemia-reperfusion (SGIR), and a sham operation group (SG). The effect of sugammadex was evaluated by measuring oxidant-antioxidant and PNL parameters. There was no significant difference in XO levels between the SGIR and GIR groups. In the SGIR group, sugammadex inhibited the increase in myeloperoxidase (MPO) and malondialdehyde (MDA) levels (p < 0.001). The amount of MDA and MPO in the SGIR group was similar as in the SG group. Sugammadex significantly suppressed the decrease in tGSH levels in the SGIR group (p < 0.001). The difference between tGSH levels in the SG and SGIR groups was slight. In the SGIR group, sugammadex significantly suppressed the increase in tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL1-β) levels compared to the GIR group (p < 0.001). Additionally, sugammadex corrected histopathological modifications as much as sham group. In conclusion, sugammadex may be beneficial in preventing oxidative stress.

Delen, Leman Acun; Dişli, Zeliha Korkmaz; Taş, Hakan G.; Kuyrukluyildiz, Ufuk; Yazici, Gulce N.; Süleyman, Bahadir; Kuzucu, Mehmet; Gürsu, Cebrail; Suleyman, Halis

Propofol may cause an increase in reactive oxygen species in the body. In this study, we tested the effect of antioxidant thiamine pyrophosphate (TPP) on propofol-induced liver damage. The eighteen rats were split into three groups: HG, healthy; PP, propofol-treated (50 mg/kg) and PT, treated with propofol (50 mg/kg) and TPP (25 mg/kg). Total glutathione (tGSH), total oxidant (TOS), and total antioxidant (TAS) levels were tested together with aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and malondialdehyde (MDA). Histopathological examination of the tissues was performed. We have found that levels of MDA, TOS, ALT, AST, and LDH were all higher in PP group than in HG and PT groups (p < 0.05). In PP group, the TAS and tGSH levels were statistically substantially lower. The PT for oxidants levels showed a statistically significant reduction. In PT group, the levels of antioxidants were found to be considerably higher. The epitheliums, glands, and vascular structures of the PTs were histologically close to normal. By boosting antioxidants, TPP may help to reduce propofol-induced liver damage.

Ekinci, Bilge; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Ozcicek, Adalet; Ergul, Cetin; Gulaboglu, Mine; Hayme, Serhat; Suleyman, Halis

Cyclooxygenase 2 (COX-2) is responsible for the therapeutic effects of indomethacin, while inhibition of the COX-1 enzyme and oxidative stress are responsible for its gastro-toxic effects. It has been reported that pycnogenol increases the expression of COX-1, suppresses the expression rate of COX-2 and oxidative stress. Our aim in this study is to investigate the antiinflammatory activities of indomethacin, pycnogenol, and their combination (PI) in rats and to examine their effects on stomach tissue. In the study, anti-inflammatory activity was investigated in carrageenan-induced inflammatory paw edema in albino Wistar male rats. Effects on stomach tissue were performed by applying the previous method. PI, indomethacin and pycnogenol were the best suppressors of carrageenan inflammation and oxidative stress in paw tissue, respectively. While the groups with the lowest COX-1 activity in paw tissue were IC, PIC and PC, respectively, PIC, IC and PC were the ones that best inhibited the increase in COX-2 activity. Pycnogenol inhibited the increase of malondialdehyde, the decrease of total glutathione and COX-1 in the stomach, and significantly suppressed the formation of indomethacin ulcers. Our experimental results showed that pycnogenol reduced the toxic effect of indomethacin on the stomach and increased anti-inflammatory activity. This beneficial interaction of pycnogenol and indomethacin suggests that PI will provide superior success in the treatment of inflammatory diseases.

Balcı, Serdar; Çöllüoğlu, Çağdaş; Yavuzer, Bülent; Bulut, Seval; Altındağ, Fikret; Akbaş, Nergis; Süleyman, Halis

Favipiravir is a drug which shows antiviral activity by inhibiting RNA-dependent RNA polymerase. Favipiravir causes severe adverse effects at high doses. The aim of this study was to investigate the effects of low and high dose favipiravir on ovarian and reproductive function in female rats. The rats were divided into three groups: HG group (healthy rats), FAV-100 group (rats administered 100 mg/kg favipiravir), and FAV-400 group (rats administered 400 mg/kg favipiravir) with 12 rats in each group. Favipiravir was administered orally twice daily for 1 week. Six rats from each group were euthanized and their ovaries were removed. Oxidative and antioxidant parameters were measured in ovarian tissues and examined histopathologically. The remaining animals were kept to breed. Animals receiving favipiravir had increased oxidant content, decreased antioxidant activity, decreased histopathological damage, infertility, and gestational delay. Favipiravir treatment should be used with caution, especially in women of reproductive age.

Ince, Sefa; Ozer, Mehmet; Kadioğlu, Berrin Goktug; Kuzucu, Mehmet; Yilmaz, Sevil Karahan; Özkaraca, Mustafa; Gezer, Arzu; Suleyman, Halis

We investigated the effect of ATP’s protection against possible bevacizumab-induced ovarian damage and reproductive dysfunction in female albino Wistar rats. A total of 42 rats, 36 females, and 6 males were used in the experiment. Normal saline (0.9% NaCl) was injected as a solvent to the Bevacizumab (BVZ; n = 12) and Control (n = 6) groups. 25 mg/kg ATP was injected intraperitoneally (i.p.) to the ATP + bevacizumab (ABZ; n = 12) group. One hour after ATP and solvent administration, 10 mg/kg bevacizumab was i.p. injected to the ABZ and BVZ groups. Bevacizumab was administered once a day every two weeks; ATP was administered one a day for 30 days. At the end of this period, six rats from each group were sacrificed with high dose of anesthesia (thiopental sodium 50 mg/kg) and biochemical and histopathological examinations were performed in ovarian tissues. Mature male rats were kept in the laboratory for two months to breed the remaining female animals. The values showed that the oxidant parameters increased in the ovarian tissue of the BVZ group compared to the healthy controls and the ABZ group, while antioxidant parameters decreased. The number of breeding animals was significantly decreased in the BVZ group compared to the Control and the ABZ groups. This result suggests that ATP may be effective in preventing oxidative damage to the ovaries and infertility induced by bevacizumab.

Ata, Nahit; Kulhan, Nur G.; Kulhan, Mehmet; Turkler, Can; Kiremitli, Tunay; Kiremitli, Sevil; Cimen, Ferda Keskin; Suleyman, Halis; Toprak, Veysel

Methotrexate (MTX) is a commonly used folic acid antagonist for the treatment of neoplasia and some autoimmune diseases. Resveratrol has important anti-inflammatory, antioxidant and immunomodulatory properties. The aim of this study was to investigate the effects of resveratrol on MTX-induced ovary-damage and oxidative stress in rats. We hypothesized that supplement of resveratrol could counteract MTX-induced cytotoxicity in rat ovary. Albino Wistar female rats were randomly divided into three groups: Healthy control (HC), resveratrol + methotrexate (RMTX) and methotrexate (MTX) group. Their ovaries were removed. Biochemical and histopathological methods were utilized for evaluation of the oxidative ovary-damage. MDA was found to be higher but tGSH and SOD were lower in the ovarian tissue of the rat group administered MTX, but it is observed that these ratios are reversed in HC and in RMTX groups. MTX treatment induced ovary damage and especially pre-treatment with resveratrol provided protective effect against this MTX-induced ovary-damaged.

Kulhan, Nur Gozde; Kulhan, Mehmet; Turkler, Can; Ata, Nahit; Kiremitli, Tunay; Kiremitli, Sevil; Cimen, Ferda Keskin; Suleyman, Halis; Toprak, Veysel

The anti-cancer drugs, particularly those used in reproductive period, may cause several complications such as ovarian insufficiency and infertility. The mechanism of action of cisplatin toxicity on the ovaries is not fully described. However, further production of free oxygen radicals and reduced production of antioxidants are thought to have an effect on the occurrence of cisplatin toxicity. The aim of this study was to investigate the effects of lycopene on cisplatin-induced ovary-damage, oxidative stres and histological changes in rats. Albino Wistar female rats were randomly divided into three groups. The control group (Group 1) received sunflower oil; animals in Group 2 received only cisplatin; one hour of lycopene pre-treatment was applied to the animals in Group 3 before administration of cisplatin. Cisplatin (5 mg/kg/day) was intraperitoneally injected as a single dose and lycopene (0.5 mg/kg/day) was administered by gavage. Biochemical and histopathological methods were utilised for evaluation of the oxidative ovary-damage. There was an increase in the levels of malondialdehyde, while total glutathione, glutathione reductase, and superoxide dismutase were decreased in Group 3, but it is observed that these ratios are reversed in the Group 1 and in the Group 2. Lycopene had protective effect against cisplatin-induced ovary-damaged.

Turkler, Can; Onat, Taylan; Yildirim, Engin; Kaplan, Selcuk; Yazici, Gulce N.; Mammadov, Renad; Sunar, Mukadder

The objective of this study is to investigate the effects of nimesulide on ketamine-induced ovarian and uterine toxicity by biochemical and histopathological examinations. Ketamine is an anesthetic agent whose use leads to overproduction of catecholamines. Nimesulide is a cyclooxy-genase-2 inhibitor, which has also been reported to exert a significant antioxidant effect. Wistar albino female rats were randomly divided into three groups as follows: ketamine group (60 mg/ kg), ketamine (60 mg/kg)+nimesulide (50 mg/kg) group, and a healthy control group. Then, the biochemical levels and histopathological findings in the ovaries and uteri of the rats were examined for malondialdehyde, myeloperoxidase, total glutathione and superoxide dismutase. The study demonstrated that, in the uterine and ovarian tissues of rats that have been administered ketamine, there was a decrease in the levels of total glutathione and superoxide dismutase, while malondialdehyde and myeloperoxidase was increased: however it was observed that these ratios were reversed in the ketamine+nimesulide group. It was also proved that the negative effects of ketamine can be corrected with nimesulide when the myometrial and endometrial thicknesses are compared. Antioxidants such as nimesulide may protect against the damage caused by ketamine to the genital organs in young women.